This work was supported by Onderzoekstoelagen grant OT/13/090 of the KU Leuven and by grant G0A3114N of the FWO-Vlaanderen.

NOT: Bu bölümde açıklanan tüm deneysel prosedürler Kurumsal Hayvan Bakım ve Leuven Katolik Üniversitesi Araştırma Danışma Kurulu tarafından onaylanmıştır (Proje: 154/2013-B De Geest). Sol Ön İnen Koroner Arter 1. Daimi ligasyonu <ol><li> / Kg sodyum pentobarbital, 70 mg ila 40 mg / kg karın içinden tatbikat ile fare anestezisi. Artık sağlam bir ayak tutam tepki fare anestezi onun doğru uçağı ulaşır emin olun. Her zaman doğru anesthetization herhangi bir cerrahi işlem veya müdahale öncesinde bu şekilde onaylayın. Anestezi altında iken korneanın kuruluğunu önlemek için oftalmik merhem yağlama kullanın. Prosedür (buprenorfin 0.05 mg / kg SQ) başlamadan önce preoperatif analjezi 2-4 saat sağlayın. <ol><li> Sağkalım ameliyat sırasında tutarlı aseptik teknikleri uygular. Bir maksimum olası ölçüde mikrobiyal con inhibe prosedürleri uygulamakKirlilik önemli enfeksiyon veya süpürasyon oluşmaz, böylece. Bu prosedürler, bu sitenin cerrahi sitesi ve dezenfeksiyon üzerinde steril aletler ve steril malzemelerin kullanımı, cerrahi alan dezenfekte ve kürk / saç kaldırılmasını içerir. </li></ol></li><li> Bir kendi kendine elde köreltilmiş 20-gauge iğne ile fare entübe. <ol><li> Baş hiperekstansiyona ile yatar pozisyonda fare koyun. <ol><li> Boyun bölgesinde ışık odaklanın. Körelmiş bir pincet ile dilini kaldırın. gırtlak girişi açıkça görülebilir. </li><li> Direk görüş altında trakea içine gırtlak yoluyla küntleşmiş iğne geçirin. Ventilatöre fare bağlayarak doğru entübasyon değerlendirin (ul atım hacmi: 3 x vücut ağırlığı (g) + 155; frekans: min başına 120 vuruş). </li></ol></li><li> Alternatif olarak, birinci dikkatlice trakea maruz bırakılmasıyla entübasyon görselleştirme geliştirmek. <ol><li> 5 mm orta boyun kesi yapmak ve gerisadece trakea üzerinde kas dokusu. </li><li> Trakea doğrudan görüntülenmesi için bir cerrahi stereomikroskopta kullanarak entübasyon gerçekleştirin. Dil kaldırın ve trakea içine kendini hazırlanmış körelmiş 20 iğne girin. Ventilatöre fare bağlayarak doğru entübasyon onaylayın (ul atım hacmi: 3 x vücut ağırlığı (g) + 155; frekans: min başına 120 vuruş). </li></ol></li></ol></li><li> Yatar pozisyonda fare tutun ve bant ile fare sabitleyin. Hipotermi önlemek için ısıtma pedi üzerinde ameliyat. <ol><li> Tıraş ve Betadine ile cildi dezenfekte edin. Sol arka bacak ameliyat sırasında sol ventrikül daha iyi bir görünüm elde etmek için sağ arka uzuv haçlar dikkat edin. </li></ol></li><li> Sternum kadar küçük enine deri kesi olun ve altta yatan cilt ve kasların ayrı. </li><li> M kenara çekin. pektoralis minör ve m. 5-0 ipek sütür ile büyük pektoralis. </li><li> Bir i yapKörelmiş bir pincet takarak üçüncü interkostal aralıkta ncision. </li><li> Sternum ulaşıldığında kadar lateralden mediale doğru interkostal kasların altında pincet taşıyın. Cilde içeriden pincet iterek göğüs duvarı delinme. Dikkatle, sadece küçük bir makas ile pincet üzerinde interkostal kas keserek torakotomi tamamlayın. Akciğerlerin delme önlemek için bu tekniği kullanın. </li><li> Akciğerler korumak için boşluğun içine% 0.9 NaCl içine daldırılmış bir sünger koyun. Kalbin sol tarafında pozlama elde etmek interkostal uzaya bir yara serpme (göğüs retraktörü) tanıtın. Şu an itibariyle, sol atrium, sol ventrikül ve koroner arter sol ön inen stereomicroscope altında görebilir. </li><li> Sol atrium ucu altında 1 mm ilgili bir tek 6-0 prolen ligature ile koroner arter sol ön inen bir ligasyonu gerçekleştirin. Bu ilk diyagonal dalından uzak olduğunu. NOT: Alternatif, 7-0 (005 mm çapında) ya da 8-0 iplikleri (0.04 mm çapında) kullanılabilir. İğne C-1 13 mm 3/8 daire Konik Noktası iğne. Koroner arter sol ön inen Başarılı ligasyonu etkilenen bölgede bir soluk görünen miyokardiyumda sonuçlanan, hemen renk değişikliği neden olur. </li><li> Yara serpme (göğüs retraktörü) sökün. <ol><li> Interkostal alanı etrafında üç 6-0 Ti-Cron sütür yerleştirin. Sütür sıkmadan önce, göğüs boşluğundan sünger kaldırmak ve vantilatör çıkışı bloke ederek akciğerlere yeniden genişletin. Böyle yaparak, akciğerler parietal plevra ile yeniden. </li><li> Daha sonra, sıkı sütür çekin ve göğüs aşağı basarak yeniden genişleme tekrarlayın. (Göğüs basınç uygulandığında ortaya çıkan hava kabarcıkları görülmelidir) tuzlu su, küçük bir miktar ile toraks başarılı kapatma kontrol edin. </li><li> Akciğerlerin normal genişleme onaylamak için interkostal kas içinden bakın. Hem pektoralis kasları yeniden konumlandırmak bir olarak hizmet verenBir pnömotoraks önlenmesi için ekstra bariyer. </li></ol></li><li> 5-0 ipek-dikişlerle cilt kapatın. </li><li> Ventilatör fareyi çıkarın ve ısıtma yastığı kurtarma sağlar. Sternal yatma korumak için yeterli bilinci yerine kadar gözetimsiz bir hayvan bırakmayın. Tamamen iyileşene kadar diğer hayvanların şirkete ameliyat geçirmiş bir hayvan iade etmeyin. </li><li> Sürekli postoperatif analjezi (ameliyattan sonra en az 48 saat süreyle buprenorfın 0.05 mg / kg SQ BID) sağlar. </li></ol> Farelerde 2. in vivo İnvaziv hemodinamik Ölçümleri <ol><li> İşlem öncesi sinyal kaymasını en aza indirmek için, en az 30 dakika boyunca 37 ° C&#39;de steril su içinde 1.0 Fransız Millar basınç kateteri daldırın. Elektronik 2,000 Hz 0 mm Hg ve 100 mm Hg basınç sensörü ve kayıt verilerini kalibre. </li><li> 1.4 g / kg üretan intraperitonal uygulama ile anestezi yapın. Kontrol edinartık sağlam bir ayak tutam tepki fare anestezi onun doğru düzlemi ulaşır. </li><li> Yatar pozisyonda anestezi fare yerleştirin. Bant ile bacaklarda sabitleyin. Bir ısıtma yastığı ile vücut sıcaklığını muhafaza etmek ve bir rektal prob ile izleyin. Boyun bölgesini Tıraş ve tiroid bezi maruz boyun bölgesinde orta hat kesi yapmak. </li><li> Bükülmüş iğneler ile boyun Fix. </li><li> Tükürük bezi kenara çekin ve sağ karotis arter maruz. , beyaz bir iplik benzer vagus siniri, arter boyunca yatıyor. Dikkatle kavisli bir forseps kullanarak vagus sinir karotid arter ayrı. </li><li> Diğer dokulardan ayırmak için sağ karotis arter altında kavisli bir forseps geçirin. Arter çevresinde bağ dokusu çıkarın. </li><li> Sağ karotis arter altında iki 6-0 ipek telleri geçmek. Yakın baş, doğru yerleştirilir üst tel, üzerinde sıkı bir düğüm yapın ve bir kocher (distal tıkayıcı ligasyonu) ile sabitleyin. Proxi geçmekmal tel iki kez sağa sola ve 2 kochers (proksimal olmayan tıkayıcı tel) ile sabitleyin. </li><li> Steril% 0.9 NaCl bırakarak nemli karotid arter tutun. Pamuk tomurcukları ile aşırı sıvı kapalı kurulayın. </li><li> Distal ligasyonu ve proksimal olmayan tıkayıcı tel arasında 26-gauge iğne ile sağ karotis arter bir kesi yapmak. </li><li> Artere basınç sensörü tanıtın. Kan kaybı olduğunu doğrulayın. Yavaşça ileri 1,0 Fransız Millar basınç kateteri itin ve kateter klavikula altında tel dikkatle geçebileceği şekilde proksimal olmayan tıkayıcı tel ayarlayın. <ol><li> Proksimal olmayan tıkayıcı tel ayarı sırasında kan kaybını en aza indirmek. Çok kırılgan olduğu için ilerleyen süre çok fazla basınç sensörü sıkıştırmak etmeyin. Proksimal tel arteri tıkayan değil gerektiğinden, damar kan ile dolu kalmalıdır. </li></ol></li><li> Basınç sinyali kaydetmeye başlayın. Bir arteriyel basınç sinyali fluctuat70 mm Hg ve 100 bir sistolik basınç - - 120 mm Hg 60 bir diyastolik basınç arasında sağlıklı bir fare es. </li><li> Innominat arter yoluyla ve sol ventrikül içine aort yoluyla kateter yönlendirin. 120 mm Hg - ventriküler basınç 0 mm Hg ve 100 arasında dalgalanır. Kateter sol ventrikül içinde stabilize izin verin. Deney koşullarına bağlı olarak, 60 dakika, 30 dakika için sinyali kaydedilir. </li><li> Deneyin tamamlanmasından sonra, 30 dakika boyunca, Alconox% 1 kateteri ıslatmak. Milli-Q su ile kateter yıkayın. Bir köpük blok kateter saklayın. </li><li> Daha fazla analiz için kayıt yazılımı veri almak. <ol><li> Veri analizi için, basınç sinyali istikrarlı bir zaman aralığı düşünün. Ilgi kaydedilen verinin en az 10 ardışık kalp döngüleri seçin. </li><li> Kalp hızı, maksimum sistolik sol ventrikül basıncı, minimal diyastolik sol ventr analiz LabChart yazılım sürümü 8.0 veya benzeri kullanınicular basınç, izovolümetrik sol ventrikül kasılma (dP / dt max), izovolümetrik sol ventrikül gevşeme (dP / dt dk), uç-diyastolik basınç tepe oranı zirve hızı, ve hacimli sol ventrikül zaman sabiti Basınç düşüşü (tau) 7. NOT: diyastol sonu basıncı hemen izovolümetrik daralmadan kaynaklı basınç dalgalanma öncesi zaman noktasında basınç gelir. tau&#39;nun hesaplama monoexponential bozulma eğrisinin, sol ventrikül basıncı uydurma dayanır, P (t) olarak ifade edilmiştir, bu formülde, p 0, e-t / tau + b = P (t), zaman sol ventrikül basıncı, dP / dt maksimum negatif değerden sonra t ulaşıldı. Parametre b basitleştirilmiş bir yaklaşım içinde sıfır olarak kabul edilebilir teorik asimptot, karşılık gelir. Gelişmiş izovolümetrik gevşeme tau daha küçük bir değere sonuçlanır. </li></ol></li></ol&gt;

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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3, 1422-1434 (2008).</li><li>Vanden Bergh, A., Flameng, W., Herijgers, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parameters+of+ventricular+contractility+in+mice:+influence+of+load+and+sensitivity+to+changes+in+inotropic+state.">Parameters of ventricular contractility in mice: influence of load and sensitivity to changes in inotropic state.</a> Pflugers Arch. 455, 987-994 (2008).</li></ol>

None of the authors reports competing financial interests.

Miyokard yapısı ve fonksiyonu Kronik değişiklikler, kalp yetmezliği, sol ventrikül disfonksiyonu gelişimi, ilerlemesi ve çeşitli kemirgen modellerinde 12 incelenebilir. Kardiyak biçimlenme ve disfonksiyonu miyokard hasarı ile uyarılan ya da basınç aort daralma enine ikincil aşırı yüklemeyin veya dilate kardiyomiyopati 12 genetik modellerinde araştırılması olabilir olabilir. Açıkçası, kemirgen modellerinin en belirgin faydası transgenik ve hücre tipi özel ve uyarılabili...

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with the cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure1.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. In other words, ventricular remodelling concerns an alteration of the left ventricular architecture. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload (e.g., mitral insufficiency). Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure.
Loss of myocardial tissue following acute myocardial infarction results in a decreased systolic ejection and an increased left ventricular end-diastolic volume and pressure. The Frank-Starling mechanism, implying that an increased end-diastolic volume results in an increased pressure developed during systole, may help to restore cardiac output. However, the concomitant increased wall stress may induce regional hypertrophy in the non-infarcted segment, whereas in the infarcted area expansion and thinning may occur. Experimental animal studies show that the infarcted ventricle hypertrophies and that the degree of hypertrophy is dependent on the infarct size2. 
The loss of myocardial tissue following acute myocardial infarction results in a sudden increase in loading conditions. Post-infarct remodelling occurs in the setting of volume overload, since the stretched and dilated infarcted tissue increases the left ventricular volume. An increased ventricular volume not only implies increased preload (passive ventricular wall stress at the end of diastole) but also increased afterload (total myocardial wall stress during systolic ejection). Afterload is increased since the systolic radius is increased. Therefore, ventricular remodelling post-myocardial infarction is characterized by mixed features of volume overload and pressure overload.
The myocardium consists of 3 integrated components: cardiomyocytes, extracellular matrix, and the capillary microcirculation. All 3&#160;components are involved in the remodelling process. Matrix metalloproteinases produced by inflammatory cells induce degradation of intermyocyte collagen struts and cardiomyocyte slippage. This leads to infarct expansion characterized by the disproportionate thinning and dilatation of the infarct segment3. In later stages of remodelling, interstitial fibrosis is induced, which negatively affects the diastolic properties of the heart. 
The vascular and cardiomyocyte compartment in the myocardium should remain balanced in the process of ventricular remodelling to avoid tissue hypoxia4,5. Whether hypertrophy progresses to heart failure or not may be critically dependent on this balance between the vascular and cardiomyocyte compartment in the myocardium. 
A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion6. In contrast, the infarct area at 24 hours after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.

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permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure

Kalp yetmezliği, kalp istirahat veya stres sırasında hücresel oksijen gereksinimleri ile orantılı bir hızda kan pompalamak için başarısız olan bir sendromdur. Bu efor özellikle sıvı retansiyonu, nefes darlığı, yorgunluk ve, ile karakterizedir. Kalp yetmezliği büyüyen bir halk sağlığı sorunu, hastaneye önde gelen nedenidir ve mortalitenin önemli bir nedenidir. İskemik kalp hastalığı, kalp yetmezliği ana nedenidir. Sol ventriküler yeniden modellenme ventrikül yapısı, boyut ve şekil değişiklikleri ifade eder. Sol ventrikül Bu mimari biçimlenme (örneğin, sistemik arteriyel hipertansiyon veya aort darlığı), ya da volüm ile basınç yükü ile, yaralanma (örneğin, miyokard infarktüsü) tarafından uyarılır. Ventrikül yeniden şekillenme duvar stresi etkilediği için, kardiyak fonksiyonu ve kalp yetmezliği gelişimi üzerinde derin bir etkisi vardır. Sol ön descendin sürekli bağlanmasından bir modeliFarelerde g koroner arter ventriküler yeniden modellenme ve kardiyak fonksiyon post-miyokardiyal enfarktüs incelemek için kullanılmıştır. Bu model koroner arter sol ön inen geçici ligasyonu modeline kıyasla hedefleri ve patofizyolojik alaka açısından temelde farklıdır. Iskemi / reperfüzyon hasarının, bu ikinci modelde, enfarktüs ilk ölçüde reperfüzyonda miyokardiyal kurtarma etkileyen faktörler tarafından modüle edilebilir. Buna karşılık, koroner arter sol ön inen kalıcı ligasyonu 24 saat sonra enfarktüs alanı sabittir. Bu modelde kardiyak fonksiyon 1) enfarktüs genişleme, enfarktüs şifa ve skar oluşumu süreci etkilenecektir; ve 2), sol ventrikül dilatasyonu, kalp hipertrofisi, ve ventriküler yeniden eşlik eden gelişme. Koroner arter, invaziv hemodinamik mea tekniği sol ön inen kalıcı ligasyonu modeli yanındaFarelerde ümler ayrıntılı olarak sunulmuştur.

miyokard enfarktüsü ölçüde Evans mavisi / 2,3,5-trifeniltetrazolyum klorür (TTC) çift boyama ile değerlendirilebilir. TTC, NADH 8 varlığında çeşitli dehidrojenaz aktivitesi nedeniyle canlı dokular içinde koyu kırmızı 1,3,5-triphenylformazan dönüştürülen bir redoks göstergesidir., 1 ila 24 saat sonra kalbin temsili bir kesiti göstermektedir, Şekil koroner arter sol ön inen ligasyonu. Mavi-lekeli alanlar non-iskemik / Normal bölgeleri göstermektedir...

Watch this Scientific Journal Video about Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure at JoVE.com

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.

Farelerde Sol Ön İnen Koroner Arter Daimi ligasyonu: Post-miyokard Enfarktüs Remodelling ve Kalp Yetmezliği Bir Model

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

permanent-ligation-left-anterior-descending-coronary-artery-mice

Research

JoVE Journal

Medicine

27.6K Görüntüleme.  Catholic University of Leuven. Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.

Video: Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. 
Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. 
Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. 
Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical.

Numerous genetic manipulations and/or intramyocardial injections of genes, proteins, cells, and/or biomaterials are superimposed upon the dimension of time in studies of acute ischemia/ reperfusion injury and chronic remodeling in mice. This video illustrates the microsurgical procedures for ischemia/reperfusion, permanent coronary artery ligation, and intramyocardial injection studies.

Enfarktüsü bir murin Model Koroner Arter ligasyon ve intramiyokardiyal Enjeksiyon

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo.  With the advent of genetic modifications to ...

Tıp

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques include transient or permanent, focal or global ischemia models using many different animal models, with the most common being rodents.
The permanent MCA ligation method which is also referred as pMCAo in the literature is used extensively as a focal ischemia model in rodents 1-6. This method was originally described for rats by Tamura et al. in 1981 7. In this protocol a craniotomy was used to access the MCA and the proximal regions were occluded by electrocoagulation. The infarcts involve mostly cortical and sometimes striatal regions depending on the location of the occlusion. This technique is now well established and used in many laboratories 8-13. Early use of this technique led to the definition and description of &#x201C;infarct core&#x201D; and &#x201C;penumbra&#x201D; 14-16, and it is often used to evaluate potential neuroprotective compounds 10, 12, 13, 17. Although the initial studies were performed in rats, permanent MCA ligation has been used successfully in mice with slight modifications 18-20 .
This model yields reproducible infarcts and increased post-survival rates. Approximately 80% of the ischemic strokes in humans happen in the MCA area 21 and thus this is a very relevant model for stroke studies. Currently, there is a paucity of effective treatments available to stroke patients, and thus there is a need for good models to test potential pharmacological compounds and evaluate physiological outcomes. This method can also be used for studying intracellular hypoxia response mechanisms in vivo. 
Here, we present the MCA ligation surgery in a C57/BL6 mouse. We describe the pre-surgical preparation, MCA ligation surgery and 2,3,5 Triphenyltetrazolium chloride (TTC) staining for quantification of infarct volumes.

Middle cerebral artery (MCA) ligation is a technique to study focal cerebral ischemia in animal models. In this method, the middle cerebral artery is exposed by craniotomy and ligated by cauterization. This method gives highly reproducible infarct volumes and increased post-operative survival rates compared to other methods available.

Fare Daimi Orta Serebral Arter ligasyon Of Uygulama

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to ...

Modified Technique for Coronary Artery Ligation in Mice

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI we need better knowledge about pathophysiology of myocardial ischemia. This knowledge may be valuable to define new therapeutic targets for innovative cardiovascular therapies4. Experimental MI model in mice is an increasingly popular small-animal model in preclinical research in which MI is induced by means of permanent or temporary ligation of left coronary artery (LCA)5. In this video, we describe the step-by-step method of how to induce experimental MI in mice.
The animal is first anesthetized with 2% isoflurane. The unconscious mouse is then intubated and connected to a ventilator for artificial ventilation. The left chest is shaved and 1.5 cm incision along mid-axillary line is made in the skin. The left pectoralis major muscle is bluntly dissociated until the ribs are exposed. The muscle layers are pulled aside and fixed with an eyelid-retractor. After these preparations, left thoracotomy is performed between the third and fourth ribs in order to visualize the anterior surface of the heart and left lung. The proximal segment of LCA artery is then ligated with a 7-0 ethilon suture which typically induces an infarct size ~40% of left ventricle. At the end, the chest is closed and the animals receive postoperative analgesia (Temgesic, 0.3 mg/50 ml, ip). The animals are kept in a warm cage until spontaneous recovery.

The surgical procedure used to induce experimental myocardial infarction in mice begins with left thoracotomy between the third and the fourth ribs in order to visualize the anterior surface of the heart and left lung. The left coronary artery is ligated, the chest is closed and the mouse is allowed to recover spontaneously.

Fare Koroner Arter Ligasyonu için Modifiye Tekniği

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI ...

A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms at work during MI and developing effective therapeutic approaches requires methodology to reproducibly simulate the clinical incidence and reflect the pathophysiological changes associated with MI. Here, we describe a surgical method to induce MI in mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as well as permanent ligation. The major advantage of this method is to facilitate location of the left anterior descending artery (LAD) to allow for accurate ligation of this artery to induce ischemia in the left ventricle of the mouse heart. Accurate positioning of the ligature on the LAD increases reproducibility of infarct size and thus produces more reliable results. Greater precision in placement of the ligature will improve the standard surgical approaches to simulate MI in mice, thus reducing the number of experimental animals necessary for statistically relevant studies and improving our understanding of the mechanisms producing cardiac dysfunction following MI. This mouse model of MI is also useful for the preclinical testing of treatments targeting myocardial damage following MI.

We introduce a surgical method to induce experimental ischemia/reperfusion (I/R) injury to simulate myocardial infarction (MI) in mouse models that allows for more clarity in positioning of the ligation on the left anterior descending artery (LAD) to increase the reproducibility of MI experiments in mice.

Sol ön inen arter ligasyonu ile Miyokard İskemi-reperfüzyon Hasarı bir fare modeli

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by reduced blood supply to the heart, resulting in the loss of oxygen to and the ensuing necrosis of the heart muscle. The MI model has gained popularity for its use as a short-term ischemia-reperfusion model and a long-term permanent ligation model. Below, we describe a reliable method for the permanent ligation of the LAD. With mouse genetic engineering technology becoming more advanced, and with an increasing availability of quality murine surgical instruments, the mouse has become a popular model for MI surgeries. Our surgical model incorporates the use of an easily reversible anesthetic for the rapid recovery of the mouse; a minimally invasive endotracheal intubation without involving a tracheotomy; and a thoracentesis through the original thoracotomy site without creating an additional incision in the chest, as is done in some other methods, to effectively remove excess blood and air from the chest cavity. This method is comparatively less invasive than other methods, which dramatically reduces surgical and post-surgical complications and mortality and improves reproducibility.

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

We provide a reliable method for left anterior descending artery (LAD) ligation in a mouse model. This method is comparatively less invasive than other methods, involving endotracheal intubation, a left-sided thoracotomy approach, and thoracentesis. This method can be used as a model for both acute and chronic myocardial infarction (MI).

Kemirgen Sol Ön İnen (LAD) koroner arter ligasyonu: Miyokard İnfarktüsü Yönelik Gelişmiş ve Basitleştirilmiş Modeli

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

Pulmoner Arter Left Koroner arter çıkış anomalileri Erişkin Aort içine Sol Koroner Arter Doğrudan Yeniden implantasyon (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

Sol Anterior İnen Koroner Arterin Kalıcı Ligasyonu ile Murine Miyokard Enfarktüsü Modeli

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.

We sought to establish a swine model of heart failure induced by left circumflex artery blockage and rapid pacing to test the effect and safety of intramyocardial administration of stem cells for cell-based therapies.

Kök Hücre Tedavisi Için Post-miyokard Enfarktüsü Kalp Yetmezliği Domuz Modeli Oluşturma

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

Göttingen Minipigs ve Landrace Domuzlarında Kapalı Göğüs Koroner Oklüzyon/Reperfüzyon Modelinde Miyokard Sonrası Enfarktüs Kalp Yetmezliği

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

There are several differences between the right and left ventricles. However, the pathophysiology of right ventricular infarction (RVI) has not been clarified. In the present protocol, a reproducible method for RVI mouse model generation is introduced, which may provide a means to explain the mechanism of RVI.

Farelerde Sağ Koroner Arterin Kalıcı Ligasyonu ile İndüklenen Sağ Ventrikül Miyokard İnfarktüsünün Oluşumu ve Karakterizasyonu

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...